Interleukin-18 increases expression of kinases involved in tau phosphorylation in SH-SY5Y neuroblastoma cells.
Inflammatory cytokines, produced mainly by activated microglia in the brain, can enhance neuronal degeneration and the amyloid-beta-plaque production involved in Alzheimer's disease (AD). We previously demonstrated that the expression of the pro-inflammatory cytokine interleukin-18 (IL-18) colocalizes with plaques and hyperphoshorylated tau containing neurons in AD patients. Here we exposed neuron-like, differentiated SH-SY5Y neuroblastomas to IL-18 and observed that the protein levels of p35, Cdk5, GSK-3beta, and Ser15-phosphorylated p53 increased during 6 h-24 h. Tau phosphorylation and expression of cyclin G1, involved in neuronal regeneration, increased at 72 h. In vivo, over-expression of IL-18 may induce hyperphosphorylation of tau and induce cell cycle activators.
Ojala
Johanna O
JO
University of Kuopio, Institute of Clinical Medicine/Neurology, Canthia, P.O.B. 1627, FIN-70211 Kuopio, Finland. Johanna.Ojala@uku.fi
Sutinen
Elina M
EM
Salminen
Antero
A
Pirttilä
Tuula
T
D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008970:Molecular Weight; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
D020382:Interleukin-18; D016875:tau Proteins; D012694:Serine; D007770:L-Lactate Dehydrogenase; D010770:Phosphotransferases